Cortisol Testing

Cortisol Testing

Arafah BM, Nishiyama FJ, Tlaygeh H, Hejal R. Measurement of salivary cortisol concentration in the assessment of adrenal function in critically ill subjects: a surrogate marker of the circulating free cortisol. J Clin Endocrinol Metab. 2007 Aug;92(8):2965-71.

METHODS: Baseline and cosyntropin-stimulated serum (total and free) and salivary cortisol concentrations were measured, in the early afternoon, in 51 critically ill patients and healthy subjects. Patients were stratified according to their serum albumin at the time of testing: those whose serum albumin levels were 2.5 gm/dl or less vs. others whose levels were greater than 2.5 gm/dl. RESULTS: Baseline and cosyntropin-stimulated serum free cortisol levels were similar in the two groups of critically ill patients and were severalfold higher (P < 0.001) than those of healthy subjects. Similarly, baseline and cosyntropin-stimulated salivary cortisol concentrations were equally elevated in the two critically ill patient groups and were severalfold higher (P < 0.001) than those of healthy subjects. Salivary cortisol concentrations correlated well with the measured serum free cortisol levels. CONCLUSIONS: Salivary cortisol measurements are simple to obtain, easy to measure in most laboratories, and provide an indirect yet reliable and practical assessment of the serum free cortisol concentrations during critical illnesses. The concentrations of the two measures of unbound cortisol determined in two different body fluids correlated very well, regardless of the serum protein concentrations. Measurements of salivary cortisol can serve as a surrogate marker for the free cortisol in the circulation. PMID: 17535998

Ceccato F, Barbot M, Zilio M, Frigo AC, Albiger N, Camozzi V, Antonelli G, Plebani M, Mantero F, Boscaro M, Scaroni C. Screening tests for Cushing's syndrome: urinary free cortisol role measured by LC-MS/MS. J Clin Endocrinol Metab. 2015 Aug 14

INTRODUCTION AND AIM: As initial screening for Cushing's syndrome (CS) the Endocrine Society guidelines recommend one of the following: the 1-mg dexamethasone suppression test (DST), or late-night salivary cortisol (LNSC), or urinary free cortisol (UFC) measurement. We examined the diagnostic performance of the above-mentioned tests in a series of patients. MATERIALS AND METHODS: We retrospectively analyzed 137 patients with clinical conditions suggestive of hypercortisolism: 38 with confirmed CS diagnosis and 99 without (termed non-CS). UFC was measured by LC-MS/MS, while LNSC by radio-immunometric method and serum cortisol by chemiluminescence immunoassay. RESULTS: Comparing CS versus non-CS, a cutoff of 138 nmol/L after 1-mg DST revealed the best specificity (SP, 97%), while the 50 nmol/L cutoff confirmed the best sensitivity (SE, 100%); the SE and SP for LNSC >14.46 nmol/L were respectively 84% and 89%, while for UFC >170 nmol/24h [64mcg/24hr, LC/MS/MS range 0-50mcg-HHL](they were 97% and 91%. Overall, UFC revealed both a combined higher positive and a lower negative likelihood ratio among first-line tests (respectively 10.7 and 0.03). Computing a ROC-contrast analysis to compare the power of each single test with that of the others, alone or combined (DST+LNSC, DST+UFC and LNSC+UFC), or with that of all the tests together (DST+LNSC+UFC), UFC assay was at least as good as all the other possible combinations. CONCLUSIONS: Measuring UFC by LC-MS/MS achieves the best accuracy in diagnosing CS among patients presenting with suspected hypercortisolism. PMID: 26274344

Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, Choi CH, Clayton RN, Courtney CH, Gonc EN, Maghnie M, Rose SR, Soule SG, Tordjman K; Consortium for Evaluation of Corticotropin Test in Hypothalamic-Pituitary Adrenal Insufficiency. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis.J Clin Endocrinol Metab. 2008 Nov;93(11):4245-53.

CONTEXT: The diagnostic value of tests for detecting hypothalamic-pituitary adrenal insufficiency (HPAI) is controversial. OBJECTIVE: Our objective was to compare standard-dose and low-dose corticotropin tests for diagnosing HPAI. DATA SOURCES: We searched the PubMed database from 1966-2006 for studies reporting diagnostic value of standard-dose or low-dose corticotropin tests, with patient-level data obtained from original investigators. STUDY SELECTION: Eligible studies had more than 10 patients. All subjects were evaluated because of suspicion for chronic HPAI, and patient-level data were available. We excluded studies with no accepted reference standard for HPAI (insulin hypoglycemia or metyrapone test) if test subjects were in the intensive care unit or if only normal healthy subjects were used as controls. DATA EXTRACTION: We constructed receiver operator characteristic (ROC) curves using patient-level data from each study and then merged results to create summary ROC curves, adjusting for study size and cortisol assay method. Diagnostic value of tests was measured by calculating area under the ROC curve (AUC) and likelihood ratios. DATA SYNTHESIS: Patient-level data from 13 of 23 studies (57%; 679 subjects) were included in the metaanalysis. The AUC were as follows: low-dose corticotropin test, 0.92 (95% confidence interval 0.89-0.94), and standard-dose corticotropin test, 0.79 (95% confidence interval 0.74-0.84). Among patients with paired data (seven studies, 254 subjects), diagnostic value of low-dose corticotropin test was superior to standard-dose test (AUC 0.94 and 0.85, respectively; P<0.001). CONCLUSIONS: Low-dose corticotropin test was superior to standard-dose test for diagnosing chronic HPAI, although it has technical limitations. PMID: 18697868

Soule S, Van Zyl Smit C, Parolis G, Attenborough S, Peter D, Kinvig S, Kinvig T, Coetzer E. The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism.Clin Endocrinol (Oxf). 2000 Aug;53(2):221-7.

OBJECTIVE: The 1 microgram ACTH stimulation test has been advocated as a sensitive indicator of the integrity of the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism. The aim of our study was to define the normal response to 1 microgram ACTH stimulation in a control population and to study the sensitivity and specificity of the test in a group of patients with suspected pituitary disease. DESIGN: A prospective analysis of the performance of the 1 microgram ACTH stimulation test in a group of patients with pituitary disease. PATIENTS: The cortisol response to 1 microgram ACTH was evaluated in 21 normal subjects and 65 patients with pituitary disease. The patients with pituitary disease were divided into two groups according to the 11-deoxycortisol response to overnight metyrapone: normal (11-deoxycortisol > 200 nmol/l) and subnormal ACTH secretory status (11-deoxycortisol < 200 nmol/l). MEASUREMENTS: In both controls and patients, blood was sampled for cortisol at - 15, 0, + 20, + 30, + 40 and + 60 minutes after intravenous administration of 1 microgram synthetic ACTH (Synacthen(R)). The overnight metyrapone test was performed only in the subjects with pituitary disease. Metyrapone (30 mg/kg) was administered orally at 2300 h and blood was sampled at 0830 h the following morning for 11-deoxycortisol. RESULTS: The 65 patients with pituitary disease were categorized according to the 11-deoxycortisol response to metyrapone as follows: 53 normal (11-deoxycortisol > 200 nmol/l) and 12 subnormal (< 200 nmol/l). The 12 patients who failed the metyrapone test had a significantly impaired cortisol response to low dose ACTH stimulation at all time points when compared with both the control group and the pituitary patients with a normal response to metyrapone (P < 0.001). Comparing the pituitary patients who had a normal response to metyrapone and the control subjects, there was no significant difference in the cortisol response to ACTH (P > 0.05). The minimum cortisol response at 30 minutes in the 21 control subjects was 414 nmol/l and this was defined as the minimum normal cortisol response to 1 microg ACTH. Using this criterion, six of the 12 patients with a subnormal response to metyrapone had a normal cortisol response to low dose ACTH stimulation. Empirically increasing the cortisol cut-off to 600 nmol/l increased the sensitivity of the low dose ACTH test to 83%, although the specificity was reduced from 100% to only 58%. CONCLUSIONS: The normal cortisol response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency proven on metyrapone testing suggests that the 1 microgram ACTH stimulation test, like the 250 microgram-test, lacks sensitivity for the diagnosis of ACTH deficiency. PMID: 10931104